A Petri net model of granulomatous inflammation: implications for IL-10 mediated control of Leishmania donovani infection.

Experimental visceral leishmaniasis, caused by infection of mice with the protozoan parasite Leishmania donovani, is characterized by focal accumulation of inflammatory cells in the liver, forming discrete "granulomas" within which the parasite is eventually eliminated. To shed new light o...

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Autores principales:	Luca Albergante, Jon Timmis, Lynette Beattie, Paul M Kaye
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/6ce79eee3fab43d680ea6580f0726784
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spelling	oai:doaj.org-article:6ce79eee3fab43d680ea6580f07267842021-11-18T05:53:20ZA Petri net model of granulomatous inflammation: implications for IL-10 mediated control of Leishmania donovani infection.1553-734X1553-735810.1371/journal.pcbi.1003334https://doaj.org/article/6ce79eee3fab43d680ea6580f07267842013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24363630/pdf/?tool=EBIhttps://doaj.org/toc/1553-734Xhttps://doaj.org/toc/1553-7358Experimental visceral leishmaniasis, caused by infection of mice with the protozoan parasite Leishmania donovani, is characterized by focal accumulation of inflammatory cells in the liver, forming discrete "granulomas" within which the parasite is eventually eliminated. To shed new light on fundamental aspects of granuloma formation and function, we have developed an in silico Petri net model that simulates hepatic granuloma development throughout the course of infection. The model was extensively validated by comparison with data derived from experimental studies in mice, and the model robustness was assessed by a sensitivity analysis. The model recapitulated the progression of disease as seen during experimental infection and also faithfully predicted many of the changes in cellular composition seen within granulomas over time. By conducting in silico experiments, we have identified a previously unappreciated level of inter-granuloma diversity in terms of the development of anti-leishmanial activity. Furthermore, by simulating the impact of IL-10 gene deficiency in a variety of lymphocyte and myeloid cell populations, our data suggest a dominant local regulatory role for IL-10 produced by infected Kupffer cells at the core of the granuloma.Luca AlberganteJon TimmisLynette BeattiePaul M KayePublic Library of Science (PLoS)articleBiology (General)QH301-705.5ENPLoS Computational Biology, Vol 9, Iss 11, p e1003334 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Biology (General) QH301-705.5
spellingShingle	Biology (General) QH301-705.5 Luca Albergante Jon Timmis Lynette Beattie Paul M Kaye A Petri net model of granulomatous inflammation: implications for IL-10 mediated control of Leishmania donovani infection.
description	Experimental visceral leishmaniasis, caused by infection of mice with the protozoan parasite Leishmania donovani, is characterized by focal accumulation of inflammatory cells in the liver, forming discrete "granulomas" within which the parasite is eventually eliminated. To shed new light on fundamental aspects of granuloma formation and function, we have developed an in silico Petri net model that simulates hepatic granuloma development throughout the course of infection. The model was extensively validated by comparison with data derived from experimental studies in mice, and the model robustness was assessed by a sensitivity analysis. The model recapitulated the progression of disease as seen during experimental infection and also faithfully predicted many of the changes in cellular composition seen within granulomas over time. By conducting in silico experiments, we have identified a previously unappreciated level of inter-granuloma diversity in terms of the development of anti-leishmanial activity. Furthermore, by simulating the impact of IL-10 gene deficiency in a variety of lymphocyte and myeloid cell populations, our data suggest a dominant local regulatory role for IL-10 produced by infected Kupffer cells at the core of the granuloma.
format	article
author	Luca Albergante Jon Timmis Lynette Beattie Paul M Kaye
author_facet	Luca Albergante Jon Timmis Lynette Beattie Paul M Kaye
author_sort	Luca Albergante
title	A Petri net model of granulomatous inflammation: implications for IL-10 mediated control of Leishmania donovani infection.
title_short	A Petri net model of granulomatous inflammation: implications for IL-10 mediated control of Leishmania donovani infection.
title_full	A Petri net model of granulomatous inflammation: implications for IL-10 mediated control of Leishmania donovani infection.
title_fullStr	A Petri net model of granulomatous inflammation: implications for IL-10 mediated control of Leishmania donovani infection.
title_full_unstemmed	A Petri net model of granulomatous inflammation: implications for IL-10 mediated control of Leishmania donovani infection.
title_sort	petri net model of granulomatous inflammation: implications for il-10 mediated control of leishmania donovani infection.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/6ce79eee3fab43d680ea6580f0726784
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A Petri net model of granulomatous inflammation: implications for IL-10 mediated control of Leishmania donovani infection.

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